Spontaneous Regression of Vitreoretinal Lymphoma Lesions: Case Series and Literature Review

PURPOSE: To describe a case series of spontaneous regression of vitreoretinal lymphoma (VRL) lesions documented through multimodal imaging and to contextualize findings with a review of the literature. METHODS: We report five Caucasian patients with biopsy-confirmed VRL. All patients underwent multimodal imaging, including spectral-domain optical coherence tomography (SD-OCT), ultra-widefield (UWF) pseudocolor, and autofluorescence (AF) imaging, and fluorescein angiography (FA). Clinical and imaging data were reviewed to assess the occurrence of spontaneous lesion regression. RESULTS: Spontaneous regression of VRL lesions was observed both in treatment-naïve patients and in patients under surveillance following prior systemic or intravitreal therapy. In one case, bilateral regression of optic nerve infiltration was observed; in two cases, unilateral regression of subretinal or sub-RPE lesions occurred; and in two cases, retinitis-like lesions spontaneously regressed. CONCLUSIONS: Spontaneous regression of VRL is a rare but clinically relevant phenomenon that may follow diagnostic interventions such as vitrectomy, possibly via immune-mediated mechanisms. Multimodal imaging is essential for documenting regression and guiding clinical management. Awareness of this phenomenon may prevent misinterpretation of disease activity and inform the need for close follow-up, even when apparent lesion regression occurs.